Immune-Cell Plasticity
We solve medical mysteries by treating unusual inflammatory diseases as natural experiments in biology. Neutrophilic dermatoses and granulomatous diseases generate large biological signals in human tissue. We use these diseases to discover how tissue-derived cues and genetic lesions reshape immune-cell identity, inflammatory architecture, and tissue repair.
One major focus of our laboratory is understanding how specificity is generated within the innate immune system. Neutrophils have traditionally been viewed as short-lived effector cells with limited plasticity. Our work challenged this view by identifying a population of long-lived APC-like neutrophils and tracing their emergence to a skin-derived signal, serum amyloid A1. This discovery showed that local tissue environments can epigenetically and functionally reprogram innate immune cells.
In parallel, our study of Sweet syndrome showed that a disease historically viewed as a nonspecific reactive process could be driven by a neutrophil-specific PIK3R1 mutation that selectively increases IL-1 receptor expression, establishing a model for genetically specified neutrophilic inflammation.
Together, these studies suggest that neutrophilic inflammation is not simply an excess of generic neutrophil activity. It can reflect precise tissue-instructed and genetically specified programs that reveal fundamental principles of innate immunity.
Granuloma Self-Organization
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Fibrosis versus Regeneration